Browsing by Subject "Tissue Plasminogen Activator"

Now showing 1 - 16 of 16
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    Association Between Thrombolytic Door-to-Needle Time and 1-Year Mortality and Readmission in Patients With Acute Ischemic Stroke.
    (JAMA, 2020-06) Man, Shumei; Xian, Ying; Holmes, DaJuanicia N; Matsouaka, Roland A; Saver, Jeffrey L; Smith, Eric E; Bhatt, Deepak L; Schwamm, Lee H; Fonarow, Gregg C
    Importance:Earlier administration of intravenous tissue plasminogen activator (tPA) in acute ischemic stroke is associated with reduced mortality by the time of hospital discharge and better functional outcomes at 3 months. However, it remains unclear whether shorter door-to-needle times translate into better long-term outcomes. Objective:To examine whether shorter door-to-needle times with intravenous tPA for acute ischemic stroke are associated with improved long-term outcomes. Design, Setting, and Participants:This retrospective cohort study included Medicare beneficiaries aged 65 years or older who were treated for acute ischemic stroke with intravenous tPA within 4.5 hours from the time they were last known to be well at Get With The Guidelines-Stroke participating hospitals between January 1, 2006, and December 31, 2016, with 1-year follow-up through December 31, 2017. Exposures:Door-to-needle times for intravenous tPA. Main Outcomes and Measures:The primary outcomes were 1-year all-cause mortality, all-cause readmission, and the composite of all-cause mortality or readmission. Results:Among the 61 426 patients treated with tPA within 4.5 hours, the median age was 80 years and 43.5% were male. The median door-to-needle time was 65 minutes (interquartile range, 49-88 minutes). The 48 666 patients (79.2%) who were treated with tPA and had door-to-needle times of longer than 45 minutes, compared with those treated within 45 minutes, had significantly higher all-cause mortality (35.0% vs 30.8%, respectively; adjusted HR, 1.13 [95% CI, 1.09-1.18]), higher all-cause readmission (40.8% vs 38.4%; adjusted HR, 1.08 [95% CI, 1.05-1.12]), and higher all-cause mortality or readmission (56.0% vs 52.1%; adjusted HR, 1.09 [95% CI, 1.06-1.12]). The 34 367 patients (55.9%) who were treated with tPA and had door-to-needle times of longer than 60 minutes, compared with those treated within 60 minutes, had significantly higher all-cause mortality (35.8% vs 32.1%, respectively; adjusted hazard ratio [HR], 1.11 [95% CI, 1.07-1.14]), higher all-cause readmission (41.3% vs 39.1%; adjusted HR, 1.07 [95% CI, 1.04-1.10]), and higher all-cause mortality or readmission (56.8% vs 53.1%; adjusted HR, 1.08 [95% CI, 1.05-1.10]). Every 15-minute increase in door-to-needle times was significantly associated with higher all-cause mortality (adjusted HR, 1.04 [95% CI, 1.02-1.05]) within 90 minutes after hospital arrival, but not after 90 minutes (adjusted HR, 1.01 [95% CI, 0.99-1.03]), higher all-cause readmission (adjusted HR, 1.02; 95% CI, 1.01-1.03), and higher all-cause mortality or readmission (adjusted HR, 1.02 [95% CI, 1.01-1.03]). Conclusions and Relevance:Among patients aged 65 years or older with acute ischemic stroke who were treated with tissue plasminogen activator, shorter door-to-needle times were associated with lower all-cause mortality and lower all-cause readmission at 1 year. These findings support efforts to shorten time to thrombolytic therapy.
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    Axonal regrowth after spinal cord injury via chondroitinase and the tissue plasminogen activator (tPA)/plasmin system.
    (The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011-10) Bukhari, Noreen; Torres, Luisa; Robinson, John K; Tsirka, Stella E
    Spinal cord injury (SCI) causes permanent debilitation due to the inability of axons to grow through established scars. Both the sugar chains and core proteins of chondroitin sulfate proteoglycans (CSPGs) are inhibitory for neurite regrowth. Chondroitinase ABC (ChABC) degrades the sugar chains and allows for synaptic plasticity, suggesting that after the sugar chain cleavage additional steps occur promoting a permissive microenvironment in the glial scar region. We report that the clearance of the core protein by the tissue plasminogen activator (tPA)/plasmin proteolytic system partially contributes to ChABC-promoted plasticity. tPA and plasmin are upregulated after SCI and degrade the deglycosylated CSPG proteins. Mice lacking tPA (tPA(-/-)) exhibit attenuated neurite outgrowth and blunted sensory and motor recovery despite ChABC treatment. Coadministration of ChABC and plasmin enhanced the tPA(-/-) phenotype and supported recovery in WT SCI mice. Collectively, these findings show that the tPA/plasmin cascade may act downstream of ChABC to allow for synergistic sensory and motor improvement compared with each treatment alone and suggest a potential new approach to enhance functional recovery after SCI.
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    Changes in Informed Consent Policy and Treatment Delays in Stroke Thrombolysis.
    (Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2020-12-18) Xu, Hanzhang; De Silva, Deidre Anne; Woon, Fung Peng; Ong, Marcus Eng Hock; Matchar, David B; Bettger, Janet Prvu; Laskowitz, Daniel T; Xian, Ying

    Objectives

    The efficacy of thrombolytic therapy with tissue plasminogen activator (tPA) is highly time dependent. Although clinical guidelines do not recommend written informed consent as it may cause treatment delays, local policy can supersede and require it. From 2014 to 2017, three out of five public hospitals in Singapore changed from written to verbal consent at different time points. We aimed to examine the association of hospital policy changes regarding informed consent on door-to-needle (DTN) times.

    Materials and methods

    Using data from the Singapore Stroke Registry and surveys of local practice, we analyzed data of 915 acute ischemic stroke patients treated with tPA within 3 hours in all public hospitals between July 2014 to Dec 2017. Patient-level DTN times before and after policy changes were examined while adjusting for clinical characteristics, within-hospital clustering, and trends over time.

    Results

    Patient characteristics and stroke severity were similar before and after the policy changes. Overall, the median DTN times decreased from 68 to 53 minutes after the policy changes. After risk adjustment, changing from written to verbal informed consent was associated with a 5.6 minutes reduction (95% CI 1.1-10.0) in DTN times. After the policy changed, the percentage of patients with DTN ≤60 minutes and ≤45 minutes increased from 35.6% to 66.1% (adjusted OR 1.75; 95% CI 1.12-2.74) and 9.3% to 36.0% (adjusted OR 2.42; 95% CI 1.37-4.25), respectively.

    Conclusion

    Changing from written to verbal consent is associated with significant improvement in the timeliness of tPA administration in acute ischemic stroke.
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    Comparison of Clinical Care and In-Hospital Outcomes of Asian American and White Patients With Acute Ischemic Stroke.
    (JAMA neurology, 2019-04) Song, Sarah; Liang, Li; Fonarow, Gregg C; Smith, Eric E; Bhatt, Deepak L; Matsouaka, Roland A; Xian, Ying; Schwamm, Lee H; Saver, Jeffrey L
    Importance:Although overall stroke incidence and mortality in the United States is improving, little is known about the characteristics and clinical outcomes of acute ischemic stroke in Asian American individuals. Objective:To compare the characteristics, care, and outcomes of Asian American and white patients with acute ischemic stroke. Design, Setting, Participants:Retrospective analysis of Asian American and white patients admitted with a primary diagnosis of acute ischemic stroke to hospitals participating in the Get With The Guidelines-Stroke (GWTG-Stroke) program between April 1, 2004, and July 31, 2016. The GWTG-Stroke database is a prospectively collected stroke quality improvement registry sponsored by the American Heart Association/American Stroke Association. Main Outcomes and Measures:Multivariable logistic regression models assessed the association of Asian American race/ethnicity, clinical outcomes, and quality measures. Results:The study population of 1 772 299 patients (mean [SD] age, 72.4 [14.2] years; 51.3% female) consisted of 64 337 Asian American patients (3.6%) and 1 707 962 white patients (96.4%) admitted to 2171 GWTG-Stroke hospitals with acute ischemic stroke. After adjustment for patient and hospital variables, Asian American patients were seen with greater stroke severity compared with white patients (National Institutes of Health Stroke Scale [NIHSS] score ≥16) (odds ratio [OR], 1.35; 95% CI, 1.30-1.40; P < .001), manifested higher in-hospital mortality (OR, 1.14; 95% CI, 1.09-1.19; P < .001), had longer length of stay (OR, 1.17; 95% CI, 1.14-1.20; P < .001), and were less likely to ambulate independently at discharge (OR, 0.84; 95% CI, 0.79-0.90; P < .001). Although Asian American patients had fewer intravenous tissue plasminogen activator (IV tPA) administrations than white patients (OR, 0.95; 95% CI, 0.91-0.98; P = .003), they had more symptomatic hemorrhage after tPA (OR, 1.36; 95% CI, 1.20-1.55; P < .001) and overall post-tPA complications (OR, 1.31; 95% CI, 1.18-1.46; P < .001). Asian American patients had better quality measure adherence overall than white patients, including rehabilitation (OR, 1.27; 95% CI, 1.18-1.36; P < .001), door to tPA within 60 minutes (OR, 1.14; 95% CI, 1.06-1.22; P < .001), and intensive statin therapy (OR, 1.14; 95% CI, 1.10-1.18; P < .001). After adjustment for stroke severity, Asian American patients had lower in-hospital mortality than white patients (OR, 0.95; 95% CI, 0.91-0.99; P = .008). Conclusions and Relevance:Asian American patients manifested more severe ischemic strokes, were less likely to receive IV tPA, and had worse functional outcomes than white patients. These findings warrant additional research toward improving clinical outcomes for Asian American patients with acute ischemic stroke.
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    Development and initial testing of the stroke rapid-treatment readiness tool.
    (J Neurosci Nurs, 2014-10) Olson, DaiWai M; Cox, Margueritte; Constable, Mark; Britz, Gavin W; Lin, Cheryl B; Zimmer, Louise O; Fonarow, Gregg C; Schwamm, Lee H; Peterson, Eric D
    No instruments are currently available to help health systems identify target areas for reducing door-to-needle times for the administration of intravenous tissue plasminogen activator to eligible patients with ischemic stroke. A 67-item Likert-scale survey was administered by telephone to stroke personnel at 252 U.S. hospitals participating in the "Get With The Guidelines-Stroke" quality improvement program. Factor analysis was used to refine the instrument to a four-factor 29-item instrument that can be used by hospitals to assess their readiness to administer intravenous tissue plasminogen activator within 60 minutes of patient hospital arrival.
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    Emergency medical services use and its association with acute ischaemic stroke evaluation and treatment in Singapore.
    (Stroke and vascular neurology, 2020-06) Xu, Hanzhang; Xian, Ying; Woon, Fung Peng; Bettger, Janet Prvu; Laskowitz, Daniel T; Ng, Yih Yng; Ong, Marcus Eng Hock; Matchar, David Bruce; De Silva, Deidre Anne

    Background

    Emergency medical services (EMS) is a critical link in the chain of stroke survival. We aimed to assess EMS use for stroke in Singapore, identify characteristics associated with EMS use and the association of EMS use with stroke evaluation and treatment.

    Methods

    The Singapore Stroke Registry combines nationwide EMS and public hospital data for stroke cases in Singapore. Multivariate regressions with the generalised estimating equations were performed to examine the association between EMS use and timely stroke evaluation and treatment.

    Results

    Of 3555 acute ischaemic patients with symptom onset within 24 hours admitted to all five public hospitals between 2015 and 2016, 68% arrived via EMS. Patients who used EMS were older, were less likely to be female, had higher stroke severity by National Institute of Health Stroke Scale and had a higher prevalence of atrial fibrillation or peripheral arterial disease. Patients transported by EMS were more likely to receive rapid evaluation (door-to-imaging time ≤25 min 34.3% vs 11.1%, OR=2.74 (95% CI 1.40 to 5.38)) and were more likely to receive intravenous tissue plasminogen activator (tPA, 22.8% vs 4.6%, OR=4.61 (95% CI 3.52 to 6.03)). Among patients treated with tPA, patients who arrived via EMS were more likely to receive timely treatment than self-transported patients (door-to-needle time ≤60 min 52.6% vs 29.4%, OR=2.58 (95% CI 1.35 to 4.92)).

    Conclusions

    EMS use is associated with timely stroke evaluation and treatment in Singapore. Seamless EMS-Hospital stroke pathways and targeted public campaigns to advocate for appropriate EMS use have the potential to improve acute stroke care.
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    Hospital distance, socioeconomic status, and timely treatment of ischemic stroke.
    (Neurology, 2019-08) Ader, Jeremy; Wu, Jingjing; Fonarow, Gregg C; Smith, Eric E; Shah, Shreyansh; Xian, Ying; Bhatt, Deepak L; Schwamm, Lee H; Reeves, Mathew J; Matsouaka, Roland A; Sheth, Kevin N
    OBJECTIVE:To determine whether lower socioeconomic status (SES) and longer home to hospital driving time are associated with reductions in tissue plasminogen activator (tPA) administration and timeliness of the treatment. METHODS:We conducted a retrospective observational study using data from the Get With The Guidelines-Stroke Registry (GWTG-Stroke) between January 2015 and March 2017. The study included 118,683 ischemic stroke patients age ≥18 who were transported by emergency medical services to one of 1,489 US hospitals. We defined each patient's SES based on zip code median household income. We calculated the driving time between each patient's home zip code and the hospital where he or she was treated using the Google Maps Directions Application Programing Interface. The primary outcomes were tPA administration and onset-to-arrival time (OTA). Outcomes were analyzed using hierarchical multivariable logistic regression models. RESULTS:SES was not associated with OTA (p = 0.31) or tPA administration (p = 0.47), but was associated with the secondary outcomes of onset-to-treatment time (OTT) (p = 0.0160) and in-hospital mortality (p = 0.0037), with higher SES associated with shorter OTT and lower in-hospital mortality. Driving time was associated with tPA administration (p < 0.001) and OTA (p < 0.0001), with lower odds of tPA (0.83, 0.79-0.88) and longer OTA (1.30, 1.24-1.35) in patients with the longest vs shortest driving time quartiles. Lower SES quintiles were associated with slightly longer driving time quartiles (p = 0.0029), but there was no interaction between the SES and driving time for either OTA (p = 0.1145) or tPA (p = 0.6103). CONCLUSIONS:Longer driving times were associated with lower odds of tPA administration and longer OTA; however, SES did not modify these associations.
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    Outcomes After Endovascular Thrombectomy With or Without Alteplase in Routine Clinical Practice.
    (JAMA neurology, 2022-08) Smith, Eric E; Zerna, Charlotte; Solomon, Nicole; Matsouaka, Roland; Mac Grory, Brian; Saver, Jeffrey L; Hill, Michael D; Fonarow, Gregg C; Schwamm, Lee H; Messé, Steven R; Xian, Ying

    Importance

    The effectiveness and safety of intravenous alteplase given before or concurrently with endovascular thrombectomy (EVT) is uncertain. Randomized clinical trials suggest there is little difference in outcomes but with only modest precision and insufficient power to analyze uncommon outcomes including symptomatic intracranial hemorrhage (sICH).

    Objective

    To determine whether 8 prespecified outcomes are different in patients with acute ischemic stroke treated in routine clinical practice with EVT with alteplase compared with patients treated with EVT alone without alteplase. It was hypothesized that alteplase would be associated with higher risk of sICH.

    Design, setting, and participants

    This was an observational cohort study conducted from February 1, 2019, to June 30, 2020, that included adult patients with acute ischemic stroke treated with EVT within 6 hours of time last known well, after excluding patients without information on discharge destination and patients with in-hospital stroke. Participants were recruited from Get With The Guidelines-Stroke, a large nationwide registry of patients with acute ischemic stroke from 555 hospitals in the US.

    Exposures

    Intravenous alteplase or no alteplase.

    Main outcomes and measures

    Prespecified outcomes were discharge destination, independent ambulation at discharge, modified Rankin score at discharge, discharge mortality, cerebral reperfusion according to modified Thrombolysis in Cerebral Infarction grade, and sICH.

    Results

    There were 15 832 patients treated with EVT (median [IQR] age, 72.0 [61.0-82.0] years; 7932 women [50.1%]); 10 548 (66.7%) received alteplase and 5284 (33.4%) did not. Patients treated with alteplase were younger, arrived via Emergency Medical Services sooner, were less likely to have certain comorbidities, including atrial fibrillation, hypertension, and diabetes, but had similar National Institutes of Health Stroke Severity (NIHSS) scores. Compared with patients who did not receive alteplase treatment, patients treated with alteplase were less likely to die (11.1% [1173 of 10 548 patients] vs 13.9% [734 of 5284 patients]; adjusted odds ratio [aOR] 0.83; 95% CI, 0.77-0.89; P < .001), more likely to have no major disability based on modified Rankin scale of 2 or less at discharge (28.5% [2415 of 8490 patients] vs 20.7% [894 of 4322 patients]; aOR, 1.36; 95% CI, 1.28-1.45; P < .001), and to have better reperfusion based on modified Thrombolysis in Cerebral Infarction grade 2b or greater (90.9% [8474 of 9318 patients] vs 88.0% [4140 of 4705 patients]; aOR, 1.39; 95% CI, 1.28-1.50; P < .001). However, alteplase treatment was associated with higher risk of sICH (6.5% [685 of 10 530 patients] vs 5.3% [279 of 5249 patients]; OR, 1.28; 95% CI, 1.16-1.42; P < .001).

    Conclusions and relevance

    In this observational cohort study of patients treated with EVT, intravenous alteplase treatment was associated with better in-hospital survival and functional outcomes but higher sICH risk after adjusting for other covariates.
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    Perception Versus Actual Performance in Timely Tissue Plasminogen Activation Administration in the Management of Acute Ischemic Stroke.
    (J Am Heart Assoc, 2015-07-22) Lin, Cheryl B; Cox, Margueritte; Olson, DaiWai M; Britz, Gavin W; Constable, Mark; Fonarow, Gregg C; Schwamm, Lee; Peterson, Eric D; Shah, Bimal R
    BACKGROUND: Timely thrombolytic therapy can improve stroke outcomes. Nevertheless, the ability of US hospitals to meet guidelines for intravenous tissue plasminogen activator (tPA) remains suboptimal. What is unclear is whether hospitals accurately perceive their rate of tPA "door-to-needle" (DTN) time within 60 minutes and how DTN rates compare across different hospitals. METHODS AND RESULTS: DTN performance was defined by the percentage of treated patients who received tPA within 60 minutes of arrival. Telephone surveys were obtained from staff at 141 Get With The Guidelines hospitals, representing top, middle, and low DTN performance. Less than one-third (29.1%) of staff accurately identified their DTN performance. Among middle- and low-performing hospitals (n=92), 56 sites (60.9%) overestimated their performance; 42% of middle performers and 85% of low performers overestimated their performance. Sites that overestimated tended to have lower annual volumes of tPA administration (median 8.4 patients [25th to 75th percentile 5.9 to 11.8] versus 10.2 patients [25th to 75th percentile 8.2 to 17.3], P=0.047), smaller percentages of eligible patients receiving tPA (84.7% versus 89.8%, P=0.008), and smaller percentages of DTN ≤60 minutes among treated patients (10.6% versus 16.6%, P=0.002). CONCLUSIONS: Hospitals often overestimate their ability to deliver timely tPA to treated patients. Our findings indicate the need to routinely provide comparative provider performance rates as a key step to improving the quality of acute stroke care.
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    Quality of Care and Outcomes for Patients With Stroke in the United States Admitted During the International Stroke Conference.
    (Journal of the American Heart Association, 2018-11) Messé, Steven R; Mullen, Michael T; Cox, Margueritte; Fonarow, Gregg C; Smith, Eric E; Saver, Jeffrey L; Reeves, Mathew J; Bhatt, Deepak L; Matsouaka, Roland; Schwamm, Lee H
    Background Patients presenting to hospitals during non-weekday hours experience worse outcomes, often attributed to reduced staffing. The American Heart Association International Stroke Conference ( ISC ) is well attended by stroke clinicians. We sought to determine whether patients with acute ischemic stroke ( AIS ) admitted during the ISC receive less guideline-adherent care and experience worse outcomes. Methods and Results We performed a retrospective cohort study of US hospitals participating in Get With The Guidelines-Stroke and assessed use of intravenous tissue plasminogen activator, other quality measures, and outcomes for patients with AIS admitted during the ISC compared with those admitted the weeks before and after the conference. A total of 69 738 patients with AIS were included: mean age, 72 years; 52% women; 29% nonwhite. There was no difference between the average weekly number of AIS cases admitted during ISC weeks versus non- ISC weeks (1984 versus 1997; P=0.95). Patient and hospital characteristics were similar between ISC and non- ISC time periods. There were no significant differences in 14 quality metrics and 5 clinical outcomes between patients with AIS treated during the ISC versus non- ISC weeks. Patients with AIS who presented within 2 hours of onset had no difference in the likelihood of receiving intravenous tissue plasminogen activator within 3 hours (adjusted odds ratio, 0.89; 95% confidence interval, 0.77-1.03; P=0.13) or the likelihood of receiving intravenous tissue plasminogen activator within 60 minutes of arrival (adjusted odds ratio, 0.92; 95% confidence interval, 0.83-1.02; P=0.13). Conclusions Patients with acute stroke admitted to Get With The Guidelines-Stroke hospitals during ISC received the same quality care and had similar outcomes as patients admitted at other times.
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    Race-Ethnic Disparities in Rates of Declination of Thrombolysis for Stroke.
    (Neurology, 2022-04) Mendelson, Scott J; Zhang, Shuaiqi; Matsouaka, Roland; Xian, Ying; Shah, Shreyansh; Lytle, Barbara L; Solomon, Nicole; Schwamm, Lee H; Smith, Eric E; Saver, Jeffrey L; Fonarow, Gregg; Holl, Jane; Prabhakaran, Shyam

    Background and objectives

    Prior regional or single-center studies have noted that 4% to 7% of eligible patients with acute ischemic stroke (AIS) decline IV tissue plasminogen activator (tPA). We sought to determine the prevalence of tPA declination in a nationwide registry of patients with AIS and to investigate differences in declination by race/ethnicity.

    Methods

    We used the Get With The Guidelines-Stroke registry to identify patients with AIS eligible for tPA and admitted to participating hospitals between January 1, 2016, and March 28, 2019. We compared patient demographics and admitting hospital characteristics between tPA-eligible patients who received and those who declined tPA. Using multivariable logistic regression, we determined patient and hospital factors associated with tPA declination.

    Results

    Among 177,115 tPA-eligible patients with AIS at 1,976 sites, 6,545 patients (3.7%) had tPA declination as the sole documented reason for not receiving tPA. Patients declining treatment were slightly older, were more likely to be female, arrived more often at off-hours and earlier after symptom onset, and were more likely to present to Primary Stroke Centers. Compared with non-Hispanic White, non-Hispanic Black race/ethnicity was independently associated with increased (adjusted odds ratio [aOR] 1.21, 95% CI 1.11-1.31), Asian race/ethnicity with decreased (aOR 0.72, 95% CI 0.58-0.88), and Hispanic ethnicity (any race) with similar odds of tPA declination (OR 0.98, 95% CI 0.86-1.13) in multivariable analysis.

    Discussion

    Although the overall prevalence of tPA declination is low, eligible non-Hispanic Black patients are more likely and Asian patients less likely to decline tPA than non-Hispanic White patients. Reducing rates of tPA declinations among non-Hispanic Black patients may be an opportunity to address disparities in stroke care.
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    Renal Dysfunction and In-Hospital Outcomes in Patients With Acute Ischemic Stroke After Intravenous Thrombolytic Therapy.
    (Journal of the American Heart Association, 2019-10-09) Rao, Zhen-Zhen; Gu, Hong-Qiu; Wang, Xian-Wei; Xie, Xue-Wei; Yang, Xin; Wang, Chun-Juan; Zhao, Xingquan; Xian, Ying; Wang, Yi-Long; Li, Zi-Xiao; Xiao, Rui-Ping; Wang, Yong-Jun; Chinese Stroke Center Alliance investigators
    Background The impact of estimated glomerular filtration rate (eGFR) on clinical short-term outcomes after stroke thrombolysis with tissue plasminogen activator remains controversial. Methods and Results We analyzed 18 320 ischemic stroke patients who received intravenous tissue plasminogen activator at participating hospitals in the Chinese Stroke Center Alliance between June 2015 and November 2017. Multivariate logistic regression models were used to evaluate associations between eGFR (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m2) and in-hospital mortality and symptomatic intracerebral hemorrhage, adjusting for patient and hospital characteristics and the hospital clustering effect. Of the 18 320 patients receiving tissue plasminogen activator, 601 (3.3%) had an eGFR <45, 625 (3.4%) had an eGFR 45 to 59, 3679 (20.1%) had an eGFR 60 to 89, and 13 415 (73.2%) had an eGFR ≥90. As compared with eGFR ≥90, eGFR values <45 (6.7% versus 0.9%, adjusted odds ratio, 3.59; 95% CI, 2.18-5.91), 45 to 59 (4.0% versus 0.9%, adjusted odds ratio, 2.00; 95% CI, 1.18-3.38), and 60 to 89 (2.5% versus 0.9%, adjusted odds ratio, 1.67; 95% CI, 1.20-2.34) were independently associated with increased odds of in-hospital mortality. However, there was no statistically significant association between eGFR and symptomatic intracerebral hemorrhage. Conclusions eGFR was associated with an increased risk of in-hospital mortality in acute ischemic stroke patients after treatment with tissue plasminogen activator. eGFR is an important predictor of poststroke short-term death but not of symptomatic intracerebral hemorrhage.
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    Risks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator.
    (JAMA neurology, 2016-01) Xian, Ying; Federspiel, Jerome J; Grau-Sepulveda, Maria; Hernandez, Adrian F; Schwamm, Lee H; Bhatt, Deepak L; Smith, Eric E; Reeves, Mathew J; Thomas, Laine; Webb, Laura; Bettger, Janet Prvu; Laskowitz, Daniel T; Fonarow, Gregg C; Peterson, Eric D
    Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, many patients may have been receiving antiplatelet therapy before acute ischemic stroke and could face an increased risk for bleeding when treated with tPA.To assess the risks and benefits associated with prestroke antiplatelet therapy among patients with ischemic stroke who receive intravenous tPA.This observational study used data from the American Heart Association and American Stroke Association Get With the Guidelines-Stroke registry, which included 85 072 adult patients with ischemic stroke who received intravenous tPA in 1545 registry hospitals from January 1, 2009, through March 31, 2015. Data were analyzed during the same period.Prestroke antiplatelet therapy before tPA administration for acute ischemic stroke.Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, discharge ambulatory status, and modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]).Of the 85 072 registry patients, 38 844 (45.7%) were receiving antiplatelet therapy before admission; 46 228 patients (54.3%) were not. Patients receiving antiplatelet therapy were older (median [25th-75th percentile] age, 76 [65-84] vs 68 [56-80] years) and had a higher prevalence of cardiovascular risk factors. The unadjusted rate of sICH was higher in patients receiving antiplatelet therapy (5.0% vs 3.7%). After risk adjustment, prior use of antiplatelet agents remained associated with higher odds of sICH compared with no use (adjusted odds ratio [AOR], 1.18 [95% CI, 1.10-1.28]; absolute difference, +0.68% [95% CI, 0.36%-1.01%]; number needed to harm [NNH], 147). Among patients enrolled on October 1, 2012, or later, the highest odds (95% CIs) of sICH were found in 15 116 patients receiving aspirin alone (AOR, 1.19 [1.06- 1.34]; absolute difference [95% CI], +0.68% [0.21%-1.20%]; NNH, 147) and 2397 patients receiving dual antiplatelet treatment of aspirin and clopidogrel (AOR, 1.47 [1.16-1.86]; absolute difference, +1.67% [0.58%-3.00%]; NNH, 60). The risk for in-hospital mortality was similar between those who were and were not receiving antiplatelet therapy after adjustment (8.0% vs 6.6%; AOR, 1.00 [0.94-1.06]; nonsignificant absolute difference, -0.01% [-0.37% to 0.36%]). However, patients receiving antiplatelet therapy had a greater risk-adjusted likelihood of independent ambulation (42.1% vs 46.6%; AOR, 1.13 [1.08-1.17]; absolute difference, +2.23% [1.55%-2.92%]; number needed to treat, 43) and better functional outcomes (modified Rankin Scale score, 0-1) at discharge (24.1% vs 27.8%; AOR, 1.14; 1.07-1.22; absolute difference, +1.99% [0.78%-3.22%]; number needed to treat, 50).Among patients with an acute ischemic stroke treated with intravenous tPA, those receiving antiplatelet therapy before the stroke had a higher risk for sICH but better functional outcomes than those who were not receiving antiplatelet therapy.
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    Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator.
    (JAMA, 2012-06) Xian, Y; Liang, L; Smith, EE; Schwamm, LH; Reeves, MJ; Olson, DM; Hernandez, AF; Fonarow, GC; Peterson, ED
    Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, patients receiving long-term chronic warfarin therapy may face an increased risk for intracranial hemorrhage when treated with tPA. Although current guidelines endorse administering intravenous tPA to warfarin-treated patients if their international normalized ratio (INR) is 1.7 or lower, there are few data on safety of intravenous tPA in warfarin-treated patients in clinical practice.To determine the risk of symptomatic intracranial hemorrhage (sICH) among patients with ischemic stroke treated with intravenous tPA who were receiving warfarin vs those who were not and to determine this risk as a function of INR.Observational study, using data from the American Heart Association Get With The Guidelines-Stroke Registry, of 23,437 patients with ischemic stroke and with INR of 1.7 or lower, treated with intravenous tPA in 1203 registry hospitals from April 2009 through June 2011.Symptomatic intracranial hemorrhage. Secondary end points include life-threatening/serious systemic hemorrhage, any tPA complications, and in-hospital mortality.Overall, 1802 (7.7%) patients with stroke treated with tPA were receiving warfarin (median INR, 1.20; interquartile range [IQR], 1.07-1.40). Warfarin-treated patients were older, had more comorbid conditions, and had more severe strokes. The unadjusted sICH rate in warfarin-treated patients was higher than in non-warfarin-treated patients (5.7% vs 4.6%, P < .001), but these differences were not significantly different after adjustment for baseline clinical factors (adjusted odds ratio [OR], 1.01 [95% CI, 0.82-1.25]). Similarly, there were no significant differences between warfarin-treated and non-warfarin-treated patients for serious systemic hemorrhage (0.9% vs 0.9%; adjusted OR, 0.78 [95% CI, 0.49-1.24]), any tPA complications (10.6% vs 8.4%; adjusted OR, 1.09 [95% CI, 0.93-1.29]), or in-hospital mortality (11.4% vs 7.9%; adjusted OR, 0.94 [95% CI, 0.79-1.13]). Among warfarin-treated patients with INRs of 1.7 or lower, the degree of anticoagulation was not statistically significantly associated with sICH risk (adjusted OR, 1.10 per 0.1-unit increase in INR [95% CI, 1.00-1.20]; P = .06).Among patients with ischemic stroke, the use of intravenous tPA among warfarin-treated patients (INR ≤1.7) was not associated with increased sICH risk compared with non-warfarin-treated patients.
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    Thrombolysis in young adults with stroke: Findings from Get With The Guidelines-Stroke.
    (Neurology, 2019-06) Dodds, Jodi A; Xian, Ying; Sheng, Shubin; Fonarow, Gregg C; Bhatt, Deepak L; Matsouaka, Roland; Schwamm, Lee H; Peterson, Eric D; Smith, Eric E
    OBJECTIVE:To determine whether young adults (≤40 years old) with acute ischemic stroke are less likely to receive IV tissue plasminogen activator (tPA) and more likely to have longer times to brain imaging and treatment. METHODS:We analyzed data from the Get With The Guidelines-Stroke registry for patients with acute ischemic stroke hospitalized between January 2009 and September 2015. We used multivariable models with generalized estimating equations to evaluate tPA treatment and outcomes between younger (age 18-40 years) and older (age >40 years) patients with acute ischemic stroke. RESULTS:Of 1,320,965 patients with acute ischemic stroke admitted to 1,983 hospitals, 2.3% (30,448) were 18 to 40 years of age. Among these patients, 12.5% received tPA vs 8.8% of those >40 years of age (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.56-1.71). However, younger patients were less likely to receive brain imaging within 25 minutes (62.5% vs 71.5%, aOR 0.78, 95% CI 0.73-0.84) and to be treated with tPA within 60 minutes of hospital arrival (37.0% vs 42.8%, aOR 0.74, 95% CI 0.68-0.79). Compared to older patients, younger patients treated with tPA had a lower symptomatic intracranial hemorrhage rate (1.7% vs 4.5%, aOR 0.55, 95% CI 0.42-0.72) and lower in-hospital mortality (2.0% vs 4.3%, aOR 0.65, 95% CI 0.52-0.81). CONCLUSIONS:In contrast to our hypothesis, younger patients with acute ischemic stroke were more likely to be treated with tPA than older patients, but they were more likely to experience delay in evaluation and treatment. Compared with older patients, younger patients had better outcomes, including fewer intracranial hemorrhages.
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    Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1.
    (The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015-09) Bukhari, Noreen; Burman, Poromendro N; Hussein, Ayan; Demars, Michael P; Sadahiro, Masato; Brady, Daniel M; Tsirka, Stella E; Russo, Scott J; Morishita, Hirofumi

    Unlabelled

    Experience-dependent cortical plasticity declines with age. At the molecular level, experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain if mice are raised in standard cages. Understanding the mechanism for the loss of permissive proteolytic activity is therefore a key link for improving function in adult brains. Using the mouse primary visual cortex (V1) as a model, we demonstrate that tPA activity in V1 can be unmasked following 4 d of monocular deprivation when the mice older than 2 months are raised in standard cages by the genetic removal of Lynx1, a negative regulator of adult plasticity. This was also associated with the reduction of stubby and thin spine density and enhancement of ocular dominance shift in adult V1 of Lynx1 knock-out (KO) mice. These structural and functional changes were tPA-dependent because genetic removal of tPA in Lynx1 KO mice can block the monocular deprivation-dependent reduction of dendritic spine density, whereas both genetic and adult specific inhibition of tPA activity can ablate the ocular dominance shift in Lynx1 KO mice. Our work demonstrates that the adult brain has an intrinsic potential for experience-dependent elevation of proteolytic activity to express juvenile-like structural and functional changes but is effectively limited by Lynx1 if mice are raised in standard cages. Insights into the Lynx1-tPA plasticity mechanism may provide novel therapeutic targets for adult brain disorders.

    Significance statement

    Experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain in correlation with the decline in cortical plasticity when mice are raised in standard cages. We demonstrated that removal of Lynx1, one of negative regulators of plasticity, unmasks experience-dependent tPA elevation in visual cortex of adult mice reared in standard cages. This proteolytic elevation facilitated dendritic spine reduction and ocular dominance plasticity in adult visual cortex. This is the first demonstration of adult brain to retain the intrinsic capacity to elevate tPA in an experience-dependent manner but is effectively limited by Lynx1. tPA-Lynx1 may potentially be a new candidate mechanism for interventions that were shown to activate plasticity in adult brain.